Functional KIR2DS4 Allele Found Increased in Chronically Infected HCV Patients is Associated with its Expression on NK and Highly Differentiated CD8+ Cells

A. PODHORZER; N. PALADINO; G. THEILER; S. PAZ; H.A. FAINBOIM; L. FAINBOIM

Congreso; 14th Meeting of the Society for Natural Immunity; 2013

Increased resolution of acute hepatitis C viral (HCV) infection was associated with individuals homozygous for KIR2DL3 and HLA-C1.However, little is known on the role play by KIR genes on the chronic infection. We analyzed the role of KIR in progression of HCVtaking into account the time of the infection.Patients: A first cohort of 235 chronically infected patients were compared with 244 healthy controls (HC). A second cohort consistedof 53 intravenous drug abusers (IDA), HIV negatives, with non blood transfusions and naïve of treatment. It is known that IDA cohortacquires HCV infection during the first year of sharing needles, criteria which led us to establish the mean time of infection for thiscohort in 25±7 years (range 13-40),Methods: All conditions to identify the presence or absence of each KIR gene, plus KIR2DS4 alleles have been previouslydocumented (Maxwell et al, 2004). HLA- A, B, and Cw genotyping was performed according to Cereb et al. and the HLA-C ligandsgroups (HLA-CAsp80 and HLA-CLys80) were also identified. The expression of KIR genes was investigated by flow cytometry in acohort of HCV patients, naïve of treatment. We used a panel of Mabs that recognize 2DL2/2DS2/2DL3, 2DL3, and 2DLI/2DS1, 2DL1,KIR2DS4, CD4, CD8, CD3 and CD56.Results: In the first cohort of chronically infected HCV patients, the frequency of KIR2DS4 was found decreased (88% Vs 95% in HC,p